title: The discovery of endothelium-dependent contraction: the legacy of Paul M. Vanhoutte.
abstract: This article summarizes the discovery and the development of endothelial biology with a special focus on the role of endothelium-dependent vasoconstriction. The physician-scientist Paul Michel Vanhoutte contributed many of the initial observations that helped to understand and form the main concepts of modern vascular biology involving endothelial regulation. His laboratory was the first to report endothelial cell-derived vasoconstriction in 1981, followed by the characterization of an endothelium-derived constricting factor published by Hickey et al. in 1985, which was later identified as the endothelin peptide by Yanagisawa et al. in 1988. The identification of the receptor subtypes of this endothelial vasocontrictor two years later, which were named ET(A) and ET(B) receptors according to suggestions put forward by Vanhoutte, ultimately resulted in the development of the only new class of drugs that is entirely based on endothelial cell research. More than a quarter century after Vanhoutte's initial description of endothelial vasoconstriction, this first drug class specifically targeting an endothelial vasoconstrictor, the endothelin receptor antagonists, has been firmly established in cardiovascular medicine for the treatment of pulmonary hypertension. This novel therapeutic principle had its beginnings in Vanhoutte's discovery made 30 years ago.
authors.affiliation: Molecular Internal Medicine, University of Zurich, LTK Y44 G22, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. barton@access.uzh.ch
authors.forename: Matthias
authors.initials: M
authors.lastname: Barton
mesh_terms: D042783:Endothelial Cells / Q000502:physiology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D016232:Endothelins / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D010455:Peptides / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000502:physiology*; D017466:Receptors, Endothelin / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D010455:Peptides; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin